Project Description Narrative:

When acute kidney injury arises as a complication of another illness or during a surgical procedure, the patient's risk of death also increases. Acute kidney injury happens in approximately 7% of hospitalized patients and about 20% of critically ill patients. Acute kidney injury, which can happen during treatments ranging from cardiac surgery to kidney transplantation, does not have any effective treatments, and clinical data have only been able to predict a small portion of patient risk. Prior research in rodents revealed the importance of genetic factors in the risk of acute kidney injury. Human studies have strengthened those findings, but have also struggled to discover which specific genes are the important ones to investigate.Through this award, researchers aim to uncover specific genes that increase the risk of acute kidney injury. By advancing this knowledge, researchers may pave the way for long-term improvement in clinical practice so that patients' risk for acute kidney injury is accurately assessed and methods for prevention are developed and implemented.

Outcomes & Lessons Learned:

• Characterized (phenotyped) the severity of acute kidney injury in 500 rats, finding a wide degree of variability in the severity of acute kidney injury in this population that mimics the variability seen in the human condition. The team then sequenced the genes of the rats to fully characterize each rats unique genetic code (genotyping)• Demonstrated that the heterogeneous stock rat model mimics the variability in severity of acute kidney injury that is observed in humans. Therefore, this model should allow researchers to more rapidly identify genes that promote kidney injury thereby enhancing the development of preventative or therapeutic treatments for kidney injury• Served as the first largescale study to use a genome-wide association approach to identify genes that modulate susceptibility to acute kidney injury in rodents. This approach bridges the gap between genome-wide association studies in humans with acute kidney injury and traditional experimental studies in rodents• Supported potential for future improvements in clinical practice by identifying new genes that increase risk for acute kidney injury and providing a genetic map to use in larger clinical studies. As studies use this map to validate methods for screening human patients for acute kidney injury risk, clinics will be better able to develop and implement methods for preventing and mitigating acute kidney injuries